Recently, effector T-cell subpopulations have been identified that can be distinguished by expression of members of the TNF-R family: CD4+OX-40+ cells are CD4 helper-effector cells CD8+CD45RA+CD27 cells are CD8-killer-effector cells. We investigated whether these lymphocyte subsets were increased in the active phase of multiple sclerosis (MS). Multiple colour immunofluorescence staining was performed on peripheral blood lymphocytes of 28 patients with active MS and of 29 healthy controls, followed by FACS analysis. Frequencies of CD8-killer-effector cells showed a wide interindividual range in both groups and percentages of CD4 helper-effector cells were low. No significant difference between the groups was observed for these subsets, but CD8+CD45RA-CD27 were increased in MS. In healthy individuals, CD4 helper-effector cells correlated with the total percentages of memory cells. Moreover, CD4+ and CD8 memory cells were strongly correlated. The here described recently identified effector CD4 and CD8 lymphocyte subpopulations were not increased in clinically active MS. It is however still possible that in MS, myelin-specific encephalitogenic cells reside within these subsets.